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The purpose of this project is to explore the benefit of using prodrugs in chemotherapy, as well as to explain the concept of angiogenesis and the importance of this process to tumor development. Angiogenesis is the formation of new blood capillaries that are necessary for the survival of a

The purpose of this project is to explore the benefit of using prodrugs in chemotherapy, as well as to explain the concept of angiogenesis and the importance of this process to tumor development. Angiogenesis is the formation of new blood capillaries that are necessary for the survival of a tumor, as a tumor cannot grow larger than 1-2 mm3 without developing its own blood supply. Vascular disrupting agents, such as iodocombstatin, a derivative of combretastatin, can be used to effectively cut off the blood supply to a growing neoplasm, effectively inhibiting the supply of oxygen and nutrients needed for cell division Thus, VDAs have a very important implication in terms of the future of chemotherapy. A prodrug, defined as an agent that is inactive in the body until metabolized to yield the drug itself, was synthesized by combining iodocombstatin with a β-glucuronide linker. The prodrug is theoretically hydrolyzed in the body to afford the active drug by β-glucuronidase, an enzyme that is produced five times as much by cancer cells as by normal cells. This effectively creates a “magic-bullet” form of chemotherapy, known as Direct Enzyme Prodrug Therapy (DEPT).
ContributorsClark, Caroline Marie (Author) / Pettit, George Robert (Thesis director) / Melody, Noeleen (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2015-05
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Description
Estimates indicate that in the United States 1 in 8 women will develop breast cancer in their lifetime. Improved cancer screenings, early detection, and targeted treatments have increased breast cancer survival rates. However, breast cancer patients treated with chemotherapy are at an increased risk for cardiovascular disease, functional impairments, and

Estimates indicate that in the United States 1 in 8 women will develop breast cancer in their lifetime. Improved cancer screenings, early detection, and targeted treatments have increased breast cancer survival rates. However, breast cancer patients treated with chemotherapy are at an increased risk for cardiovascular disease, functional impairments, and loss of cardiorespiratory fitness. These negative outcomes have implications for early morbidity and mortality. The purpose of this thesis was to test the hypothesis that high-intensity exercise preconditioning (exercise commenced prior to initiating chemotherapy and continued throughout treatment cycles) preserves health-related outcomes in breast cancer patients treated with anthracycline-containing chemotherapy. Here, we present a subset of preliminary data from an ongoing trial (NCT02842658) that is focused on VO2peak and skeletal muscle outcomes from the first 10 participants that have enrolled in the trial. Breast cancer patients (N=10; 50 ± 11 y; 168 ± 4 cm; 92 ± 37 kg; 32.3 ± 12.3 kg/m2) scheduled to receive anthracycline-containing chemotherapy were randomly assigned to one of two interventions: 1) exercise preconditioning, (3 days per week of supervised exercise throughout treatment) or 2) standard of care (attention-control). Pre-testing occurred 1-2 week prior to chemotherapy. The interventions were initiated 1 week prior to chemotherapy and continued throughout anthracycline treatment. Post-testing occurred 3-7 days following the last anthracycline treatment. VO2peak (L/min) was reduced by 16% in the control group (P < 0.05), whereas VO2peak was preserved in the exercise preconditioning group. Trends for greater preservation and/or improvement in the exercise preconditioning group were also observed for lean body mass and peak heart rate. Hand grip strength was not changed in either group (P > 0.05). Both groups demonstrated an increase in ultrasound-derived echogenicity measures of the vastus lateralis (P < 0.05), indicating changes in the composition of the skeletal muscle during treatment. These preliminary data highlight that exercise preconditioning may serve as a strategy to preserve cardiorespiratory fitness and perhaps lean mass during anthracycline treatment of breast cancer. There remains a need for larger, definitive clinical trials to identify strategies to prevent the array of chemotherapy-induced toxicities that are observed in breast cancer patients treated with anthracyclines.
ContributorsCasey, Kathleen (Author) / Angadi, Siddhartha (Thesis director) / Gaesser, Glenn (Committee member) / Dickinson, Jared (Committee member) / College of Health Solutions (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
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Description

Background:
Thirty to fifty percent of cancer patients undergoing chemotherapy will experience
chemotherapy induced nausea and or vomiting (CINV) despite the use of antiemetic prophylaxis Uncontrollable CINV can lead to complications that add extra stress to patients, increase in healthcare costs, and utilization of resources. CINV can lead to chemotherapy dose reductions,

Background:
Thirty to fifty percent of cancer patients undergoing chemotherapy will experience
chemotherapy induced nausea and or vomiting (CINV) despite the use of antiemetic prophylaxis Uncontrollable CINV can lead to complications that add extra stress to patients, increase in healthcare costs, and utilization of resources. CINV can lead to chemotherapy dose reductions, treatment delays, chemotherapy changes, or discontinuation of treatment. Guidelines exist to better prevent and treat CINV. Evidence supports the use of guidelines to prevent CINV, however patients still suffer from CINV often due to a lack of guideline adherence.

Objectives:
The purpose of this project was to increase CINV guideline adherence by increasing knowledge of antiemetic guidelines utilizing an educational intervention for providers and nurses at an outpatient oncology office.

Methods:
A brief educational intervention on CINV and recommended NCCN guidelines was
conducted with providers and nurse (n=6) at an oncology practice in Southwestern United States. An evaluation to assess change in knowledge was performed using a pre and post test format. Statistical analysis was performed using descriptive statistics, McNemar tests and Wicoxan Signed Rank Test.

Findings:
There was a significant effect on knowledge of NCCN antiemetic guidelines (Z=-1.89, p=0.059, mean 2.5) post intervention. There also was a significant impact on likelihood to use guidelines in practice (Z=-1.89, p=0.059, mean 2.5). Increasing awareness and likelihood to CHEMOTHERAPY INDUCED NAUSEA AND VOMITING 3 follow recommended guidelines may improve CINV symptoms in patients undergoing chemotherapy and improve the treatment outcomes for these patients.

ContributorsBarbosa, Jennifer (Author) / Baker, Laurie (Thesis advisor)
Created2018-04-29